Bernard Thorens received his PhD from the University of Geneva for studies on the biosynthesis of immunogluobulins in pre-B lymphocytes. He then did a first postdoctoral fellowship in Geneva working on hematopoietic growth factors with Pierre Vassalli. In 1986 he moved to the Whitehead Institute for Biomedical Research in Cambridge (USA) for a postdoctoral fellowhisp in Harvey Lodish laboratory. In 1991 he came back to Switzerland to take a Career Development award from the SNSF and to establish his laboratory at the Department of Pharmacology and Toxicology. Since 2002 he is Professor on Physiology and joined the Center for Integrative Genomics in 2005.
Glucose transporters, hormone receptors, pancreatic ß cells, hypothalamus, glucose sensing, diabetes.
Molecular and physiological analysis of energy homeostasis in health and disease
Glucose homeostasis and development of type 2 diabetes are critically dependent on the capacity of the insulin secreting beta-cells of the pancreas to secrete insulin according to the metabolic need of the organism. This secretory capacity depends on both the number and secretion capacity of the differentiated beta-cells.
One of our research projects aimed at identying novel genes that regulate beta-cell proliferation, secretion capacity and apoptosis. To this end we are evaluating the mode of action on beta-cells of the gluco-incretin hormones GLP-1 and GIP, which are known to stimulate beta-cell precursor differentiation and proliferation of mature beta-cells, as well as to protect these cells against apoptosis. Our ongoing work was initiated by performing transcript profiling of islets from mice with genetic inactivation of the GLP-1 and GIP receptors, and which showed decreased secretion capacity and increased susceptibility to apoptosis. The function of these genes is investigated by overexpression or down-expression (siRNA) studies in beta-cell lines, primary beta cells and in transgenic mice, followed by functional analysis of proliferation, apoptosis, insulin secretion, as well as whole body glucose homeostasis.
Glucose homeostasis, feeding behavior and energy expenditure are under the control of the hypothalamus, where neuronal circuits integrate internal signals, informing on food absorption and metabolic energy storage, and send new signal to regulate energy homeostasis.
In a second line of investigation we thus aim at identifying, at the cellular and molecular levels, the mechanisms by which glucose is sensed by neurons, and how these sensing neurons regulate the function of the hypothalamic neuronal circuits controlling glucose and energy homeostasis. These studies are based on the analysis of gene knockout mice, which show loss of central glucose sensing and, as a consequence, deregulated control of feeding and energy expenditure. These studies are being pursued by genetically marking the glucose sensing cells to identify them and characterize the neuronal circuits they form to control the melanocortin pathway, a key hypothalamic neuronal circuit controlling glucose and energy homeostasis. We are also generating mice with tissue and cell-specific knockout of a glucose transporter to inactivate these glucose sensors and evaluate their role in specific anatomical sites. These investigations involve the use of molecular biology techniques, immunohistochemistry, and integrated physiological analysis of control or genetically modified mice.
In a third line of investigation, we seek to identify the metaboplic pathways in liver that are associated with susceptibility or resistance to diet-induced steatosis using comparative transcriptomic and lipidodomic analysis of liver from different strains of mice. We have previously provided evidence that resistance to steatosis development was associated with increased expression of enzymes controlling peroxisomal beta-oxidation and microsomal fatty acid elongation; lipidomic analysis has demonstrated that many lipid species were differently produced in association with resistance to steatosis development. We are testing the role of these lipids in controlling insulin resistance and the proinflammatory state of the resistant mice. These studies are being pursued by combined transcriptomic, lipidomic and physiological analysis of mice with knockout of some of the identified genes. These studies will investigate the functional role of specific lipid species in controlling gene expression and the proinflammatory state, which is tightly associated with development of metabolic diseases.
Basco D, Zhang Q, Salehi A, Tarasov A, Dolci W, Herrera P, Spiliotis I, Berney X, Tarussio D, Rorsman P, Thorens B. α-cell glucokinase suppresses glucose-regulated glucagon secretion. Nat Commun. 2018 Feb 7;9(1):546
Wigger L, Cruciani-Guglielmacci C, Nicolas A, Denom J, Fernandez N, Fumeron F, Marques-Vidal P, Ktorza A, Kramer W, Schulte A, Le Stunff H, Liechti R, Xenarios I, Vollenweider P, Waeber G, Uphues I, Roussel R, Magnan C, Ibberson M, Thorens B. (2017) Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans. Cell Rep. 2017 Feb 28;18(9):2269-2279
Steinbusch LKM, Picard A, Labouèbe G, Basco D, Bonnet M, Berney X, Dolci W, Thorens B. Sex-specific control of fat mass and counterregulation by hypothalamic glucokinase. (2016) Diabetes 65 : 2920-31.
Picard A, Soyer J, Berney X, Tarussio D, Jan M, Burdet F, Ibberson M, Thorens B. A genetic screen identifies hypothalamic FGF15 as a regulator of glucagon secretion. (2016) Cell Reports 17(7):1795-1806.
Modi H, Jacovetti C, Tarussio D, Metref S, Madsen OD, Zhang FP, Rantakari P, Poutanen M, Nef S, Gorman T, Regazzi R, Thorens B. (2015) Autocrine action of IGF2 regulates adult β cell mass and function. Diabetes. 64:4148–4157.
Labouèbe G, Boutrel B, Tarussio D, Thorens B. (2016) Glucose responsive neurons of the paraventricular thalamus control sucrose-seeking behavior.Nat. Neurosci. 19 : 999-1002.
Lamy CM, Sanno H, Labouèbe G, Picard A, Magnan C, Chatton JY, Thorens B. (2014) Hypoglycemia-activated Glut2 Neurons of the Nucleus Tractus Solitarius Stimulate Vagal Activity and Glucagon Secretion. Cell Met. 19 : 527-538.
Advanced search is available through Serval
Publications can be managed by accessing Serval via MyUnil
Xavier Berney - Technician
Gwenaël Labouebe - Senior Research Assistant
After a master’s degree in computational science achieved in France, Gwenaël joined the University of Geneva where he obtained his PhD under the supervision of the Pr. Christian Lüscher working on the cellular and molecular mechanisms of dependence and addiction. In March 2009, he started a post-doctoral position with the Dr. Stephanie Borgland at the University of British Columbia where he investigated appetitive motivation disorders such as obesity and addiction. Since end of 2011 he is working as a research associate in the Prof. Thorens laboratory where he is studying the interaction between neuronal circuits involved in glucose-sensing and motivated feeding behaviors.
Alexandre Picard - Senior Research Assistant
After two years of medical studies, Alexandre continued his studies at the University of Paris 7 and received a Bachelor of cell biology and physiology and a master cell biology, physiology and pathology. He did then a thesis in the field of metabolic diseases on the study of the role of hippocampal lipoprotein lipase in the nervous regulation of energy homeostasis. Alexandre has joined the laboratory of Prof. Thorens in 2013.
Sevasti Gaspari - Post-doctoral Fellow
Sevasti has obtained a B.Sc in Biology and a M.Sc in Molecular Biology and Biomedicine at University of Crete (Greece). She continued with a Ph.D in Neurobiology in the lab of Dr. Zachariou at Icahn School of Medicine at Mount Sinai (NY), with a main focus on the role of Regulation of G-protein Signaling in chronic pain and responses to opioids. She applied murine mouse models, biochemistry and whole transcriptome analysis to investigate signal transduction adaptations in the brain associated with long term pain states, and prolonged exposure to opioids. “Staying in the brain” from now on she will be focusing on the exploration of neuronal circuits controlling feeding behavior and glucose homeostasis.
Anastasiya Strembitska - Post-doctoral Fellow
Anastasiya obtained her BSc in Biomedical Engineering at the University of Lisbon, IST, Portugal. After that she moved to Glasgow, UK, to pursue a MSc Degree in Translational Medicine and, later, PhD in Cardiovascular Sciences in Dr. Salt’s laboratory at the Glasgow University. During her PhD she studied the effect on hyperinsulinaemia and hyperglycaemia on insulin-stimulated nitric oxide production and mitochondrial phenotype in human macrovascular endothelial cells. Her research in Prof. Thorens’ group will focus on the role of mitochondria in glucose sensing in neurons and regulation of glucagon secretion.
Judit Castillo Armengol - Post-doctoral Fellow
Judit obtained her Bachelor in Biology from the University of Barcelona in 2013 and her Master’s degree in Biomedical Research from the University Pompeu Fabra (Barcelona) in 2014. Then, she joined the lab of Prof. Lluis Fajas Coll to focus on the role of cell cycle regulators in adipose tissue metabolism, where she completed her PhD in Life Sciences in 2019. Currently, she is working in the lab of Prof. Bernard Thorens as an IMI Novo Nordisk Postdoctoral Research Fellow focusing on the central control of glucose homeostasis.